• Title/Summary/Keyword: Noncoding RNA

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Role of Intergenic and 3'-Proximal Noncoding Regions in Coat Protein Expression and Replication of Barley yellow dwarf virus PAV

  • Moon, Jae-Sun;Nancy K. McCoppin;Leslie L. Domier
    • The Plant Pathology Journal
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    • v.17 no.1
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    • pp.22-28
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    • 2001
  • Barley yellow dwarf virus PAV (BYDV-PAV) has a 5.7-kb positive-sense single-stranded RNA genome that contains six open reading frames (ORFs). BYDV-PAV produces three subgenomic RNAs (sgRNAs). The largest of which encodes the coat, 17-kDa, and readthrough proteins from two initiation codons. To investigate the role of intergenic and 3'-proximal noncoding regions (NCRs) in coat protein (CP) expression and BYDV-PAV replication, a full-length infectious cDNA of the RNA genome of an Illinois isolate of BYDV-PAV was constructed downstream of the Cauliflower mosaic virus-35S promoter. Linear DNA molecules of these cDNAs were infectious, expressed the 22-kDa CP, and produced both genomic RNA sgRNAs in ratios similar to those observed in protoplasts inoculated with viral RNA. The portion of 5'NCR of sgRNA1 between ORFs 2 and 3 was not required for, but enhanced translation of CP from ORF3. Mutants containing deletions in the NCR downstream of ORF5 failed to replicate in oat protoplasts. These results indicate that an intact 3$^1$NCR is required for BYDV-PAV replication.

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FoxD2-AS1 is a prognostic factor in glioma and promotes temozolomide resistance in a O6-methylguanine-DNA methyltransferase-dependent manner

  • Shangguan, Wenbing;Lv, Xuyang;Tian, Nan
    • The Korean Journal of Physiology and Pharmacology
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    • v.23 no.6
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    • pp.475-482
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    • 2019
  • Glioma is the most common brain tumor with a dismal prognosis. While temozolomide (TMZ) based chemotherapy significantly improves survival in glioma patients, resistance against this compound commonly leads to glioma treatment failure. Overexpression of long-noncoding RNA (LncRNA) FoxD2 adjacent opposite strand RNA 1 (FoxD2-AS1) was identified to promote glioma development, but the role in TMZ resistance remains unclear. In this paper, we found that FoxD2-AS1 was overexpressed in recurrent glioma, high FoxD2-AS1 expression was significantly correlated with poor patient outcome. Methylation of $O^6$-methylguanine-DNA methyltransferase (MGMT) is significantly less frequent in high FoxD2-AS1 expression patients. Knockdown of FoxD2-AS1 decreased the proliferation, metastatic ability of glioma cells and promote the sensitivity to TMZ in glioma cells. Furthermore, knockdown of FoxD2-AS1 induced hypermethylation of the promoter region of MGMT. Our data suggested that FoxD2-AS1 is a clinical relevance LncRNA and mediates TMZ resistance by regulating the methylation status of the MGMT promoter region.

Identification of a New 5'-Noncoding Exon Region and Promoter Activity in Human N-Acetylglucosaminyltransferase III Gene

  • Kang, Bong-Seok;Kim, Yeon-Jeong;Shim, Jae-Kyoung;Song, Eun-Young;Park, Young-Guk;Lee, Young-Choon;Nam, Kyung-Soo;Kim, June-Ki;Lee, Tae-Kyun;Chung, Tae-Wha;Kim, Cheorl-Ho
    • BMB Reports
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    • v.31 no.6
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    • pp.578-584
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    • 1998
  • In a previous paper (Kim et al., 1996a), the immediate 5' -flanking region and coding region of the human UDP-N -acetylglucosamine:-D-mannoside-1,4-Nacetylglucosaminyltransferase III (N-acetylglucosaminyitransferase- III; GnT-III) gene was reported, isolated and analyzed. Herein, we report on amplification of a new 5' -noncoding region of the GnT-III mRNA by single-strand ligation to single-stranded cDNA-PCR (5' -RACE PCR) using poly(A)+ RNA isolated from human fetal liver cells. A cDNA clone was obtained with 5' sequences (96 bp) that diverged seven nucleotides upstream from the ATG (+1) start codon. A concensus splice junction sequence, TCTCCCGCAG, was found immediately 5' to the position where the sequences of the cDNA diverged. The result suggested the presence of an intron in the 5' -noncoding region and that the cDNA was an incompletely reversetranscribed cDNA product derived from an mRNA containing a new noncoding exon. When mRNA expression of GnT-III in various human tissues and cancer cell lines was examined, Northern blot analysis indicated high expression levels of GnT-III in human fetal kidney and brain tissues, as well as for a number of leukemia and lymphoma cancer cell lines. Promoter activities of the 5' -flanking regions of exon 1 and the new noncoding region were measured in a human hepatoma cell line, HepG2, by luciferase assays. The 5'-flanking region of exon 1 was the most active, whilst that of exon 2 was inactive.

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Long Noncoding RNA Expression Profiling Reveals Upregulation of Uroplakin 1A and Uroplakin 1A Antisense RNA 1 under Hypoxic Conditions in Lung Cancer Cells

  • Byun, Yuree;Choi, Young-Chul;Jeong, Yongsu;Yoon, Jaeseung;Baek, Kwanghee
    • Molecules and Cells
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    • v.43 no.12
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    • pp.975-988
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    • 2020
  • Hypoxia plays important roles in cancer progression by inducing angiogenesis, metastasis, and drug resistance. However, the effects of hypoxia on long noncoding RNA (lncRNA) expression have not been clarified. Herein, we evaluated alterations in lncRNA expression in lung cancer cells under hypoxic conditions using lncRNA microarray analyses. Among 40,173 lncRNAs, 211 and 113 lncRNAs were up- and downregulated, respectively, in both A549 and NCI-H460 cells. Uroplakin 1A (UPK1A) and UPK1A-antisense RNA 1 (AS1), which showed the highest upregulation under hypoxic conditions, were selected to investigate the effects of UPK1A-AS1 on the expression of UPK1A and the mechanisms of hypoxia-inducible expression. Following transfection of cells with small interfering RNA (siRNA) targeting hypoxia-inducible factor 1α (HIF-1α), the hypoxia-induced expression of UPK1A and UPK1A-AS1 was significantly reduced, indicating that HIF-1α played important roles in the hypoxia-induced expression of these targets. After transfection of cells with UPK1A siRNA, UPK1A and UPK1A-AS1 levels were reduced. Moreover, transfection of cells with UPK1A-AS1 siRNA downregulated both UPK1A-AS1 and UPK1A. RNase protection assays demonstrated that UPK1A and UPK1A-AS1 formed a duplex; thus, transfection with UPK1A-AS1 siRNA decreased the RNA stability of UPK1A. Overall, these results indicated that UPK1A and UPK1A-AS1 expression increased under hypoxic conditions in a HIF-1α-dependent manner and that formation of a UPK1A/UPK1A-AS1 duplex affected RNA stability, enabling each molecule to regulate the expression of the other.

The Association of Long Noncoding RNA LOC105372577 with Endoplasmic Reticulum Protein 29 Expression: A Genome-wide Association Study (ERp29 유전자 발현과 관련된 long noncoding RNA LOC105372577의 전장 유전체 연관성 분석)

  • Lee, Soyeon;Kwon, Kiang;Ko, Younghwa;Kwon, O-Yu
    • Journal of Life Science
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    • v.31 no.6
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    • pp.568-573
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    • 2021
  • This study identified genomic factors associated with endoplasmic reticulum protein (ERp)29 gene expression in a genome-wide association study (GWAS) of genetic variants, including single-nucleotide polymorphisms (SNPs). In total, 373 European genes from the 1000 Genomes Project were analyzed. SNPs with an allelic frequency of less than or more than 5% were removed, resulting in 5,913,563 SNPs including in the analysis. The following expression quantitative trait loci (eQTL) from the long noncoding RNA LOC105372577 were strongly associated with ERp29 expression: rs6138266 (p<4.172e10), rs62193420 (p<1.173e10), and rs6138267 (p<2.041e10). These were strongly expressed in the testis and in the brain. The three eQTL were identified through a transcriptome-wide association study (TWAS) and showed a significant association with ERp29 and osteosarcoma amplified 9 (OS9) expression. Upstream sequences of rs6138266 were recognized by ChIP-seq data, while HaploReg was used to demonstrate how its regulatory DNA binds upstream of transcription factor 1 (USF1). There were no changes in the expression of OS9 or USF1 following ER stress.

Temporal expression profiling of long noncoding RNA and mRNA in the peripheral blood during porcine development

  • Gu, Yiren;Zhou, Rui;Jin, Long;Tao, Xuan;Zhong, Zhijun;Yang, Xuemei;Liang, Yan;Yang, Yuekui;Wang, Yan;Chen, Xiaohui;Gong, Jianjun;He, Zhiping;Li, Mingzhou;Lv, Xuebin
    • Asian-Australasian Journal of Animal Sciences
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    • v.33 no.5
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    • pp.836-847
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    • 2020
  • Objective: We investigated the temporal expression profiles of long noncoding RNA (lncRNA) and mRNA in the peripheral blood of pigs during development and identified the lncRNAs that are related to the blood-based immune system. Methods: Peripheral blood samples were obtained from the pigs at 0, 7, 28, and 180 days and 2 years of age. RNA sequencing was performed to survey the lncRNA and mRNA transcriptomes in the samples. Short time-series expression miner (STEM) was used to show temporal expression patterns in the mRNAs and lncRNAs. Gene ontology and Kyoto encyclopedia of genes and genomes analyses were performed to assess the genes' biological relevance. To predict the functions of the identified lncRNAs, we extracted mRNAs that were nearby loci and highly correlated with the lncRNAs. Results: In total of 5,946 lncRNA and 12,354 mRNA transcripts were identified among the samples. STEM showed that most lncRNAs and mRNAs had similar temporal expression patterns during development, indicating the expressional correlation and functional relatedness between them. The five stages were divided into two classes: the suckling period and the late developmental stage. Most genes were expressed at low level during the suckling period, but at higher level during the late stages. Expression of several T-cell-related genes increased continuously during the suckling period, indicating that these genes are crucial for establishing the adaptive immune system in piglets at this stage. Notably, lncRNA TCONS-00086451 may promote blood-based immune system development by upregulating nuclear factor of activated T-cells cytoplasmic 2 expression. Conclusion: This study provides a catalog of porcine peripheral blood-related lncRNAs and mRNAs and reveals the characteristics and temporal expression profiles of these lncRNAs and mRNAs during peripheral blood development from the newborn to adult stages in pigs.

Comparison of characteristics of long noncoding RNA in Hanwoo according to sex

  • Choi, Jae-Young;Won, KyeongHye;Son, Seungwoo;Shin, Donghyun;Oh, Jae-Don
    • Asian-Australasian Journal of Animal Sciences
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    • v.33 no.5
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    • pp.696-703
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    • 2020
  • Objective: Cattle were some of the first animals domesticated by humans for the production of milk, meat, etc. Long noncoding RNA (lncRNA) is defined as longer than 200 bp in nonprotein coding transcripts. lncRNA is known to function in regulating gene expression and is currently being studied in a variety of livestock including cattle. The purpose of this study is to analyze the characteristics of lncRNA according to sex in Hanwoo cattle. Methods: This study was conducted using the skeletal muscles of 9 Hanwoo cattle include bulls, steers and cows. RNA was extracted from skeletal muscle of Hanwoo. Sequencing was conducted using Illumina HiSeq2000 and mapped to the Bovine Taurus genome. The expression levels of lncRNAs were measured by DEGseq and quantitative trait loci (QTL) data base was used to identify QTLs associated with lncRNA. The python script was used to match the nearby genes Results: In this study, the expression patterns of transcripts of bulls, steers and cows were identified. And we identified significantly differentially expressed lncRNAs in bulls, steers and cows. In addition, characteristics of lncRNA which express differentially in muscles according to the sex of Hanwoo were identified. As a result, we found differentially expressed lncRNAs according to sex were related to shear force and body weight. Conclusion: This study was classified and characterized lncRNA which differentially expressed by sex in Hanwoo cattle. We believe that the characterization of lncRNA by sex of Hanwoo will be helpful for future studies of the physiological mechanisms of Hanwoo cattle.

Nuclear Bodies Built on Architectural Long Noncoding RNAs: Unifying Principles of Their Construction and Function

  • Chujo, Takeshi;Hirose, Tetsuro
    • Molecules and Cells
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    • v.40 no.12
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    • pp.889-896
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    • 2017
  • Nuclear bodies are subnuclear, spheroidal, and membraneless compartments that concentrate specific proteins and/or RNAs. They serve as sites of biogenesis, storage, and sequestration of specific RNAs, proteins, or ribonucleoprotein complexes. Recent studies reveal that a subset of nuclear bodies in various eukaryotic organisms is constructed using architectural long noncoding RNAs (arcRNAs). Here, we describe the unifying mechanistic principles of the construction and function of these bodies, especially focusing on liquid-liquid phase separation induced by architectural molecules that form multiple weakly adhesive interactions. We also discuss three possible advantages of using arcRNAs rather than architectural proteins to build the bodies: position-specificity, rapidity, and economy in sequestering nucleic acid-binding proteins. Moreover, we introduce two recently devised methods to discover novel arcRNA-constructed bodies; one that focuses on the RNase-sensitivity of these bodies, and another that focuses on "semi-extractability" of arcRNAs.

Functional annotation of lung cancer-associated genetic variants by cell type-specific epigenome and long-range chromatin interactome

  • Lee, Andrew J.;Jung, Inkyung
    • Genomics & Informatics
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    • v.19 no.1
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    • pp.3.1-3.12
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    • 2021
  • Functional interpretation of noncoding genetic variants associated with complex human diseases and traits remains a challenge. In an effort to enhance our understanding of common germline variants associated with lung cancer, we categorize regulatory elements based on eight major cell types of human lung tissue. Our results show that 21.68% of lung cancer-associated risk variants are linked to noncoding regulatory elements, nearly half of which are cell type-specific. Integrative analysis of high-resolution long-range chromatin interactome maps and single-cell RNA-sequencing data of lung tumors uncovers number of putative target genes of these variants and functionally relevant cell types, which display a potential biological link to cancer susceptibility. The present study greatly expands the scope of functional annotation of lung cancer-associated genetic risk factors and dictates probable cell types involved in lung carcinogenesis.